Amelioration of experimental colitis after short-term therapy with glucocorticoid and its relationship to the induction of different regulatory markers

Autor(es)

Sales-Campos, Helioswilton ; de Souza, Patricia R. ; Basso, Paulo J. ; Nardini, Viviani ; Silva, Angelica ; Banquieri, Fernanda ; Alves, Vanessa B. F. ; Chica, Javier E. L. ; Nomizo, Auro ; Cardoso, Cristina R. B.

• Tipo de documento: Artigo Científico
• Fonte: IMMUNOLOGY; v. 150, n. 1, p. 12-pg., 2017-01-01.

Resumo

The clinical benefits of short-term therapy with glucocorticoids (GC) in patients with inflammatory bowel disease (IBD) are widely known. However, the effects of this treatment towards the re-establishment of the regulatory network in IBD are not fully explored. We have evaluated the immunological effects of the abbreviated GC therapy in experimental colitis induced by 3% dextran sulphate sodium in C57BL/6 mice. Treatment with GC improved disease outcome, constrained circulating leucocytes and ameliorated intestinal inflammation. The control of the local inflammatory responses involved a reduction in the expression of interferon-gamma and interleukin-1 beta, associated with augmented mRNA levels of peroxisome proliferator-activated receptors (alpha and gamma) in intestine. Furthermore, there was a reduction of CD4(+) T cells producing interferon-gamma, together with an increased frequency of the putative regulatory population of T cells producing interleukin-10, in spleen. These systemic alterations were accompanied by a decrease in the proliferative potential of splenocytes of mice treated in vivo with GC. Notably, treatment with GC also led to an increase in the frequency of the regulatory markers GITR, CTLA-4, PD-1, CD73 and FoxP3, more prominently in spleen. Taken together, our results pointed to a role of GC in the control of leucocyte responsiveness and re-establishment of a regulatory system, which probably contributed to disease control and the restoration of immune balance. Finally, this is the first time that GC treatment was associated with the modulation of a broad number of regulatory markers in an experimental model of colitis. (AU)

• Processo FAPESP: 12/00984-8 - Participação do eixo hipotálamo-pituitária-adrenal na Doença Inflamatória Intestinal induzida experimentalmente
• Beneficiário: Patrícia Reis de Souza
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 10/20162-7 - Papel do eixo hipotálamo-pituitária adrenal e glicocorticóides exógenos na modulação da resposta imune na doença inflamatória intestinal
• Beneficiário: Cristina Ribeiro de Barros Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores